tbuckley/cabot-search huggingface dataset:
Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial
Authors: Felix C Ringshausen, Adam J Shapiro, Kim G Nielsen, Henryk Mazurek, Massimo Pifferi, Karl H Donn, Menno M van der Eerden, Michael R Loebinger, Maimoona A Zariwala, Margaret W Leigh, Michael R Knowles, Thomas W Ferkol, Felix C Ringshausen, Adam J Shapiro, Kim G Nielsen, Henryk Mazurek, Massimo Pifferi, Karl H Donn, Menno M van der Eerden, Michael R Loebinger, Maimoona A Zariwala, Margaret W Leigh, Michael R Knowles, Thomas W Ferkol, Jr, Trey Brown, Mary Carroll, Nina Church, Marisa Couluris, Stephanie D Davis, Sharon D Dell, Maria E Di Cicco, Angela Di Mango, Hugo Escobar, Anne Griffiths, Kenan Haver, Douglas Hornick, Christopher Johnson, Carlos E Milla, Anne O'Donnell, Isabell Pink, Andrzej Pogorzelski, Michelle Prickett, Benjamin A Raby, Margaret Rosenfeld, Thomas G Saba, Rikke Mulvad Sandvik, Scott D Sagel, Matthias Salathe, Ashley E Simmons, George M Solomon, Olaf Sommerburg, Najwa Soussi, Steven D Strausbaugh, Kelli M Sullivan, Claudius Werner
Journal: The Lancet Respiratory Medicine (2023)
Outcomes of repeat transcatheter aortic valve replacement with balloon-expandable valves: a registry study
Authors: Raj R Makkar, Samir Kapadia, Tarun Chakravarty, Robert J Cubeddu, Tsuyoshi Kaneko, Paul Mahoney, Dhairya Patel, Aakriti Gupta, Wen Cheng, Susheel Kodali, Deepak L Bhatt, Michael J Mack, Martin B Leon, Vinod H Thourani
Journal: The Lancet (2023)
Gout incidence and management during the COVID-19 pandemic in England, UK: a nationwide observational study using OpenSAFELY
Authors: Mark D Russell, Jon Massey, Edward Roddy, Brian MacKenna, Seb Bacon, Ben Goldacre, Colm D Andrews, George Hickman, Amir Mehrkar, Arti Mahto, Andrew I Rutherford, Samir Patel, Maryam A Adas, Edward Alveyn, Deepak Nagra, Katie Bechman, Joanna M Ledingham, Joanna Hudson, Sam Norton, Andrew P Cope, James B Galloway
Journal: The Lancet Rheumatology (2023)

Gout is the most prevalent inflammatory arthritis, yet one of the worst managed. Our objective was to assess how the COVID-19 pandemic impacted incidence and quality of care for people with gout in England, UK.
Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial
Authors: Marc E Rothenberg, Evan S Dellon, Margaret H Collins, Ikuo Hirano, Mirna Chehade, Albert J Bredenoord, Alfredo J Lucendo, Jonathan M Spergel, Xian Sun, Jennifer D Hamilton, Eric Mortensen, Elizabeth Laws, Jennifer Maloney, Leda P Mannent, Eilish McCann, Xia Liu, Lila Glotfelty, Arsalan Shabbir
Journal: The Lancet. Gastroenterology & hepatology (2023)
In vivo CRISPR gene editing in patients with herpetic stromal keratitis
Authors: Anji Wei, Di Yin, Zimeng Zhai, Sikai Ling, Huangying Le, Lijia Tian, Jianjiang Xu, Soren R. Paludan, Yujia Cai, Jiaxu Hong
Journal: Molecular Therapy (2023)
Age-Dependent Female Survival Advantage in Hepatocellular Carcinoma: A Multicenter Cohort Study
Authors: Chuan Pang, Jian-Ming Li, Zhen Wang, Yan-Chun Luo, Zhi-Gang Cheng, Zhi-Yu Han, Fang-Yi Liu, Xiao-Ling Yu, Feng Liang, Hong-Qing Xi, Rong-Qin Zheng, Wen Cheng, Qiang Wei, Song-Yuan Yu, Qin-Ying Li, Guang-Zhi He, Jie Yu, Ping Liang
Journal: Clinical Gastroenterology and Hepatology (2023)
Gas station in blood vessels: An endothelium mimicking, self-sustainable nitric oxide fueling stent coating for prevention of thrombosis and restenosis
Authors: Jingdong Rao, Xiaohui Mou, Yongyi Mo, Ho-Pan Bei, Li Wang, Chuyang Y. Tang, Kai-Hang Yiu, Zhilu Yang, Xin Zhao
Journal: Biomaterials (2023)
Genetic characterization of Klebsiella pneumoniae carbapenemase -producing Klebsiella pneumoniae isolates with different susceptibility to ceftazidime/avibactam in patients with blood-stream infections
Authors: Flavia Badalucco Ciotta, Francesca Saluzzo, Alessandra Pescò, Federico Di Marco, Silvia Carletti, Marco Ripa, Nicasio Mancini, Daniela M. Cirillo, Antonella Castagna, Chiara Oltolini
Journal: Clinical Microbiology and Infection (2023)
Is colchicine prophylaxis required with start-low go-slow allopurinol dose escalation in gout? A non-inferiority randomised double-blind placebo-controlled trial
Authors: Lisa Stamp, Anne Horne, Borislav Mihov, Jill Drake, Janine Haslett, Peter T Chapman, Christopher Frampton, Nicola Dalbeth
Journal: Annals of the Rheumatic Diseases (2023)

To determine whether placebo is non-inferior to low-dose colchicine for reducing gout flares during the first 6 months of allopurinol using the 'start-low go-slow' dose approach.A 12-month double-blind, placebo-controlled non-inferiority trial was undertaken. Adults with at least one gout flare in the preceding 6 months, fulfilling the American College of Rheumatology (ACR) recommendations for starting urate-lowering therapy and serum urate ≥0.36 mmol/L were recruited. Participants were randomised 1:1 to colchicine 0.5 mg daily or placebo for the first 6 months. All participants commenced allopurinol, increasing monthly to achieve target urate <0.36 mmol/L. The primary efficacy outcome was the mean number of gout flares/month between 0 and 6 months, with a prespecified non-inferiority margin of 0.12 gout flares/month. The primary safety outcome was adverse events over the first 6 months.Two hundred participants were randomised. The mean (95% CI) number of gout flares/month between baseline and month 6 was 0.61 (0.47 to 0.74) in the placebo group compared with 0.35 (0.22 to 0.49) in the colchicine group, mean difference 0.25 (0.07 to 0.44), non-inferiority p=0.92. There was no difference in the mean number of gout flares/month between randomised groups over the 12-month period (p=0.68). There were 11 serious adverse events in 7 participants receiving colchicine and 3 in 2 receiving placebo.Placebo is not non-inferior to colchicine in prevention of gout flares in the first 6 months of starting allopurinol using the 'start-low go-slow' strategy. After stopping colchicine, gout flares rise with no difference in the mean number of gout flares/month between groups over a 12-month period.ACTRN 12618001179224.
<scp>Sex‐Linked</scp> Discrepancies in <scp>C57BL6</scp>/J Mouse Osteoarthritis are Associated With the Gut Microbiome and are Transferrable by Microbiome Transplantation
Authors: Leoni Schlupp, Emmaline Prinz, Gabriella Dyson, Montana Barrett, Vladislav Izda, Christopher M. Dunn, Matlock A. Jeffries
Journal: Arthritis & Rheumatology (2023)

Females have reduced osteoarthritis (OA) in surgical models. The objective of the current study was to evaluate a sex-linked gut microbiome in the pathogenesis of OA.
Covid-19 and flu boosters to start earlier than planned, with extra funding for GPs
Authors: Gareth Iacobucci
Journal: BMJ (2023)

Covid-19 and flu boosters to start earlier than with extra funding for GPs Gareth IacobucciThe government has reversed its decision to delay England's covid and influenza vaccination campaigns for adults this year, citing the identification of a new covid variant as the reason.1
Molecular basis for potent B cell responses to antigen displayed on particles of viral size
Authors: Jeremy F. Brooks, Julianne Riggs, James L. Mueller, Raisa Mathenge, Wei-Yun Wholey, Alexander R. Meyer, Sekou-Tidiane Yoda, Vivasvan S. Vykunta, Hailyn V. Nielsen, Wei Cheng, Julie Zikherman
Journal: Nature Immunology (2023)
Original SARS-CoV-2 monovalent and Omicron BA.4/BA.5 bivalent COVID-19 mRNA vaccines: phase 2/3 trial interim results
Authors: Spyros Chalkias, Jordan L. Whatley, Frank Eder, Brandon Essink, Shishir Khetan, Paul Bradley, Adam Brosz, Nichole McGhee, Joanne E. Tomassini, Xing Chen, Xiaoping Zhao, Andrea Sutherland, Xiaoying Shen, Bethany Girard, Darin K. Edwards, Jing Feng, Honghong Zhou, Stephen Walsh, David C. Montefiori, Lindsey R. Baden, Jacqueline M. Miller, Rituparna Das
Journal: Nature Medicine (2023)

This ongoing, open-label, phase 2/3 trial compared the safety and immunogenicity of the Omicron BA.4/BA.5-containing bivalent mRNA-1273.222 vaccine with the ancestral Wuhan-Hu-1 mRNA-1273 as booster doses. Two groups of adults who previously received mRNA-1273 as primary vaccination series and booster doses were enrolled in a sequential, nonrandomized manner and received single-second boosters of mRNA-1273 (n = 376) or bivalent mRNA-1273.222 (n = 511). Primary objectives were safety and the noninferiority or superiority of neutralizing antibody (nAb) responses against Omicron BA.4/BA.5 and ancestral SARS-CoV-2 with the D614G mutation (ancestral SARS-CoV-2 (D614G)), 28 days post boost. Superiority and noninferiority were based on prespecified success criteria (lower bounds of 95% CI > 1 and < 0.677, respectively) of the mRNA-1273.222:mRNA-1273 geometric mean ratios. Bivalent Omicron BA.4/BA.5-containing mRNA-1273.222 elicited superior nAb responses against BA.4/BA.5 versus mRNA-1273 and noninferior responses against ancestral SARS-CoV-2 (D614G) at day 29 post boost in participants without detectable prior SARS-CoV-2 infection. Day 29 seroresponses against Omicron BA.4/BA.5 were higher for mRNA-1273.222 than for mRNA-1273 and similar against ancestral SARS-CoV-2 (D614G), both meeting noninferiority criterion. The safety profile of mRNA-1273.222 was similar to that previously reported for mRNA-1273 with no new safety concerns identified. Continued monitoring of neutralization and real-world vaccine effectiveness are needed as additional divergent-virus variants emerge. ClinicalTrials.gov registration: NCT04927065.
Profiling of repetitive RNA sequences in the blood plasma of patients with cancer
Authors: Roman E. Reggiardo, Sreelakshmi Velandi Maroli, Vikas Peddu, Andrew E. Davidson, Alexander Hill, Erin LaMontagne, Yassmin Al Aaraj, Miten Jain, Stephen Y. Chan, Daniel H. Kim
Journal: Nature Biomedical Engineering (2023)

Abstract Liquid biopsies provide a means for the profiling of cell-free RNAs secreted by cells throughout the body. Although well-annotated coding and non-coding transcripts in blood are readily detectable and can serve as biomarkers of disease, the overall diagnostic utility of the cell-free transcriptome remains unclear. Here we show that RNAs derived from transposable elements and other repeat elements are enriched in the cell-free transcriptome of patients with cancer, and that they serve as signatures for the accurate classification of the disease. We used repeat-element-aware liquid-biopsy technology and single-molecule nanopore sequencing to profile the cell-free transcriptome in plasma from patients with cancer and to examine millions of genomic features comprising all annotated genes and repeat elements throughout the genome. By aggregating individual repeat elements to the subfamily level, we found that samples with pancreatic cancer are enriched with specific Alu subfamilies, whereas other cancers have their own characteristic cell-free RNA profile. Our findings show that repetitive RNA sequences are abundant in blood and can be used as disease-specific diagnostic biomarkers.
Sex differences in brain protein expression and disease
Authors: Aliza P. Wingo, Yue Liu, Ekaterina S. Gerasimov, Selina M. Vattathil, Jiaqi Liu, David J. Cutler, Michael P. Epstein, Gabriëlla A. M. Blokland, Madhav Thambisetty, Juan C. Troncoso, Duc M. Duong, David A. Bennett, Allan I. Levey, Nicholas T. Seyfried, Thomas S. Wingo
Journal: Nature Medicine (2023)

Abstract Most complex human traits differ by sex, but we have limited insight into the underlying mechanisms. Here, we investigated the influence of biological sex on protein expression and its genetic regulation in 1,277 human brain proteomes. We found that 13.2% (1,354) of brain proteins had sex-differentiated abundance and 1.5% (150) of proteins had sex-biased protein quantitative trait loci (sb-pQTLs). Among genes with sex-biased expression, we found 67% concordance between sex-differentiated protein and transcript levels; however, sex effects on the genetic regulation of expression were more evident at the protein level. Considering 24 psychiatric, neurologic and brain morphologic traits, we found that an average of 25% of their putatively causal genes had sex-differentiated protein abundance and 12 putatively causal proteins had sb-pQTLs. Furthermore, integrating sex-specific pQTLs with sex-stratified genome-wide association studies of six psychiatric and neurologic conditions, we uncovered another 23 proteins contributing to these traits in one sex but not the other. Together, these findings begin to provide insights into mechanisms underlying sex differences in brain protein expression and disease.
A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases
Authors: Wagner S. Brum, Nicholas C. Cullen, Shorena Janelidze, Nicholas J. Ashton, Eduardo R. Zimmer, Joseph Therriault, Andrea L. Benedet, Nesrine Rahmouni, Cécile Tissot, Jenna Stevenson, Stijn Servaes, Gallen Triana-Baltzer, Hartmuth C. Kolb, Sebastian Palmqvist, Erik Stomrud, Pedro Rosa-Neto, Kaj Blennow, Oskar Hansson
Journal: Nature Aging (2023)

Cost-effective strategies for identifying amyloid-β (Aβ) positivity in patients with cognitive impairment are urgently needed with recent approvals of anti-Aβ immunotherapies for Alzheimer's disease (AD). Blood biomarkers can accurately detect AD pathology, but it is unclear whether their incorporation into a full diagnostic workflow can reduce the number of confirmatory cerebrospinal fluid (CSF) or positron emission tomography (PET) tests needed while accurately classifying patients. We evaluated a two-step workflow for determining Aβ-PET status in patients with mild cognitive impairment (MCI) from two independent memory clinic-based cohorts (n = 348). A blood-based model including plasma tau protein 217 (p-tau217), age and APOE ε4 status was developed in BioFINDER-1 (area under the curve (AUC) = 89.3%) and validated in BioFINDER-2 (AUC = 94.3%). In step 1, the blood-based model was used to stratify the patients into low, intermediate or high risk of Aβ-PET positivity. In step 2, we assumed referral only of intermediate-risk patients to CSF Aβ42/Aβ40 testing, whereas step 1 alone determined Aβ-status for low- and high-risk groups. Depending on whether lenient, moderate or stringent thresholds were used in step 1, the two-step workflow overall accuracy for detecting Aβ-PET status was 88.2%, 90.5% and 92.0%, respectively, while reducing the number of necessary CSF tests by 85.9%, 72.7% and 61.2%, respectively. In secondary analyses, an adapted version of the BioFINDER-1 model led to successful validation of the two-step workflow with a different plasma p-tau217 immunoassay in patients with cognitive impairment from the TRIAD cohort (n = 84). In conclusion, using a plasma p-tau217-based model for risk stratification of patients with MCI can substantially reduce the need for confirmatory testing while accurately classifying patients, offering a cost-effective strategy to detect AD in memory clinic settings.
Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization
Authors: Maxime Taquet, Zuzanna Skorniewska, Adam Hampshire, James D. Chalmers, Ling-Pei Ho, Alex Horsley, Michael Marks, Krisnah Poinasamy, Betty Raman, Olivia C. Leavy, Matthew Richardson, Omer Elneima, Hamish J. C. McAuley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Ruth M. Saunders, Victoria C. Harris, Linzy Houchen-Wolloff, Neil J. Greening, Parisa Mansoori, Ewen M. Harrison, Annemarie B. Docherty, Nazir I. Lone, Jennifer Quint, Naveed Sattar, Christopher E. Brightling, Louise V. Wain, Rachael E. Evans, John R. Geddes, Paul J. Harrison
Journal: Nature Medicine (2023)

Post-COVID cognitive deficits, including 'brain fog', are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized with COVID-19, we identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19. A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety. Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits.
Erratum: Vol. 71, No. 48
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

In the report "Appliances Used by Consumers to Prepare Frozen Stuffed Chicken Products -United States, May-July 2022," on page 1511, in the fifth paragraph, the second and third sentences should have read, "Respondents reporting preparing the product, compared with those who did not prepare the product, included a higher proportion of men (50.8% versus 44.4%), and a lower proportion of respondents aged ≥60 years (29.1% versus 35.1%).A lower proportion of respondents who lived in the U.S. Census Bureau West Region (21.8% versus 27.4%) reported preparing the product, compared with those who did not prepare the product."
Outbreak of Multidrug-Resistant Tuberculosis — Kansas, 2021–2022
Authors: Elizabeth Groenweghe, Lauren Swensson, Kimberly D. Winans, Phillip Griffin, Maryam B. Haddad, Richard J. Brostrom, Dawn Tuckey, Chee Kin Lam, Lisa Y. Armitige, Barbara J. Seaworth, Erin A. Corriveau
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

An outbreak of multidrug-resistant (MDR) tuberculosis (TB) involved 13 persons in four households in a low-income, under-resourced urban Kansas community during November 2021-November 2022.A majority of the seven adults identified in the Kansas outbreak were born outside the United States in a country that had experienced an MDR TB outbreak with the same genotype during 2007-2009, whereas most of the six children in the Kansas outbreak were U.S.-born.Prompt identification, evaluation, and treatment of persons with MDR TB and their contacts is essential to limiting transmission.
Posttranslational ISGylation of NLRP3 by HERC enzymes facilitates inflammasome activation in models of inflammation
Authors: Ying Qin, Xintong Meng, Mengge Wang, Wenbo Liang, Rong Xu, Jingchunyu Chen, Hui Song, Yue Fu, Jingxin Li, Chengjiang Gao, Mutian Jia, Chunyuan Zhao, Wei Zhao
Journal: Journal of Clinical Investigation (2023)

The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a crucial component of the innate immune system that initiates inflammatory responses. Post-translational modifications (PTMs) of NLRP3, including ubiquitination and phosphorylation, control inflammasome activation and determine the intensity of inflammation. However, the role of other PTMs in controlling NLRP3 inflammasome activation remains unclear. This study founded that toll-like receptor (TLR) priming induced NLRP3 ISGylation (a type of PTM in which ISG15 covalently binds to the target protein) to stabilise the NLRP3 protein. Viral infection, represented by SARS-COV-2 infection, and type I IFNs induced the expression of ISG15 and the predominant E3 ISGylation ligases HECT domain- and RCC1-like domain-containing proteins (HERCs; HERC5 in humans and HERC6 in mice). HERCs promoted NLRP3 ISGylation and inhibited K48-linked ubiquitination and proteasomal degradation, resulting in the enhancement of NLRP3 inflammasome activation. Concordantly, Herc6 deficiency ameliorated NLRP3-dependent inflammation, and hyperinflammation caused by viral infection. These results illustrate the mechanism by which type I IFNs responses control inflammasome activation and viral infection-induced aberrant NLRP3 activation. This work identifies ISGylation as a PTM of NLRP3 and provides a priming target for modulating NLRP3-dependent immunopathology.
Nonfatal and Fatal Falls Among Adults Aged ≥65 Years — United States, 2020–2021
Authors: Ramakrishna Kakara, Gwen Bergen, Elizabeth Burns, Mark Stevens
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

In the United States, unintentional falls are the leading cause of injury and injury death among adults aged ≥65 years (older adults). Patterns of nonfatal and fatal falls differ by sex and state. To describe this variation, data from the 2020 Behavioral Risk Factor Surveillance System and 2021 National Vital Statistics System were used to ascertain the percentage of older adults who reported falling during the previous year and unintentional fall-related death rates among older adults. Measures were stratified by demographic characteristics, U.S. Census Bureau region, and state. In 2020, 14 million (27.6%) older adults reported falling during the previous year. The percentage of women who reported falling (28.9%) was higher than that among men (26.1%). The percentage of older adults who reported falling ranged from 19.9% (Illinois) to 38.0% (Alaska). In 2021, 38,742 (78.0 per 100,000 population) older adults died as the result of unintentional falls. The unintentional fall-related death rate was higher among men (91.4 per 100,000) than among women (68.3). The fall-related death rate among older adults ranged from 30.7 per 100,000 (Alabama) to 176.5 (Wisconsin). CDC's Stopping Elderly Accidents, Deaths and Injuries (STEADI) initiative recommends that health care providers screen and assess older adults for fall risk and intervene using effective preventive strategies.